| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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Purity: ≥98%
Pralnacasan (VX-740; HMR-3480) is a novel, potent, selective, and orally bioactive non-peptide inhibitor of caspase 1 (IL-1beta converting enzyme) with a Ki of 1.4 nM and with the potential for the treatment of osteoarthritis and rheumatoid arthritis. It is able to inhibit proinflammatory cytokines IL-18, IL-1β , and IFN-γ.
| ln Vivo |
Joint injury was lessened by pralnacasan (0–50 mg/kg; oral gavage; twice daily; for 6 weeks; female Balb/c mice). Animal body weight does not seem to be impacted by pranacadasan therapy [1].
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| Animal Protocol |
Animal/Disease Models: Collagenase-induced female balb/c (Bagg ALBino) mouse [1]
Doses: 0 mg/kg, 12.5 mg/kg, 25 mg/kg and 50 mg/kg Route of Administration: po (oral gavage); twice a day; continuous 6-week Experimental Results: Histopathological lesions in the medial compartment of the knee improved Dramatically. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Orally bioavailable |
| References |
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| Additional Infomation |
Pralnacasan is an orally bioavailable pro-drug of a potent, non-peptide inhibitor of interleukin-1beta converting enzyme (ICE).
Drug Indication For the treatment of rheumatoid arthritis (RA). Mechanism of Action Pralnacasan inhibits interleukin-1beta converting enzyme (ICE), an enzyme that regulates the production of IL-1 and IFN gamma - intercellular mediators that initiate and sustain the process of inflammation. Inhibiting ICE may be an effective strategy for curtailing damaging inflammatory processes common to a number of acute and chronic conditions, such as rheumatoid arthritis (RA) and osteoarthritis. Pharmacodynamics Pralnacasan is a potent, non-peptide inhibitor of interleukin-1beta converting enzyme (ICE). Pralnacasan is an oral, anti-cytokine drug candidate licensed for development by Aventis Pharma from Vertex Pharmaceuticals. In November 2003, Aventis and Vertex Pharmaceuticals announced that they had voluntarily suspended the phase II clinical trials of pralnacasan due to results from an animal toxicity study that demonstrated liver abnormalities after a nine-month exposure to pralnacasan at high doses. While no similar liver toxicity has been seen to date in human trials, the companies will evaluate the animal toxicity results before proceeding with the phase II clinical program. |
| Molecular Formula |
C26H29N5O7
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|---|---|
| Molecular Weight |
523.53776
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| Exact Mass |
523.207
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| CAS # |
192755-52-5
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| PubChem CID |
153270
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| Appearance |
White to off-white solid powder
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| Density |
1.44g/cm3
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| Index of Refraction |
1.657
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| LogP |
1.762
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
38
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| Complexity |
960
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CCO[C@H]1[C@H](CC(=O)O1)NC(=O)[C@@H]2CCCN3N2C(=O)[C@H](CCC3=O)NC(=O)C4=NC=CC5=CC=CC=C54
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| InChi Key |
CXAGHAZMQSCAKJ-WAHHBDPQSA-N
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| InChi Code |
InChI=1S/C26H29N5O7/c1-2-37-26-18(14-21(33)38-26)29-23(34)19-8-5-13-30-20(32)10-9-17(25(36)31(19)30)28-24(35)22-16-7-4-3-6-15(16)11-12-27-22/h3-4,6-7,11-12,17-19,26H,2,5,8-10,13-14H2,1H3,(H,28,35)(H,29,34)/t17-,18-,19-,26+/m0/s1
|
| Chemical Name |
(1S,9S)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)-9-(isoquinoline-1-carboxamido)-6,10-dioxooctahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxamide
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| Synonyms |
VX740 HMR 3480 VX 740 HMR-3480 VX-740 HMR3480
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~220 mg/mL (~420.22 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.5 mg/mL (10.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 55.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5.5 mg/mL (10.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 55.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5.5 mg/mL (10.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9101 mL | 9.5504 mL | 19.1007 mL | |
| 5 mM | 0.3820 mL | 1.9101 mL | 3.8201 mL | |
| 10 mM | 0.1910 mL | 0.9550 mL | 1.9101 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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